Kidney Modelling for FDG Excretion with PET

The purpose of this study was to detect the physiological process of FDG's filtration from blood to urine and to establish a mathematical model to describe the process. Dynamic positron emission tomography scan for FDG was performed on seven normal volunteers. The filtration process in kidney can be seen in the sequential images of each study. Variational distribution of FDG in kidney can be detected in dynamic data. According to the structure and function, kidney is divided into parenchyma and pelvis. A unidirectional three-compartment model is proposed to describe the renal function in FDG excretion. The time-activity curves that were picked up from the parenchyma, pelvis, and abdominal aorta were used to estimate the parameter of the model. The output of the model has fitted well with the original curve from dynamic data

Compartmental analysis of dynamic nuclear medicine data: models and identifiability

Compartmental models based on tracer mass balance are extensively used in clinical and pre-clinical nuclear medicine in order to obtain quantitative information on tracer metabolism in the biological tissue. This paper is the first of a series of two that deal with the problem of tracer coefficient estimation via compartmental modelling in an inverse problem framework. Specifically, here we discuss the identifiability problem for a general n-dimension compartmental system and provide uniqueness results in the case of two-compartment and three-compartment compartmental models. The second paper will utilize this framework in order to show how non-linear regularization schemes can be applied to obtain numerical estimates of the tracer coefficients in the case of nuclear medicine data corresponding to brain, liver and kidney physiology

The next era of renal radionuclide imaging: novel PET radiotracers

Although single-photon-emitting radiotracers have long been the standard for renal functional molecular imaging, recent years have seen the development of positron emission tomography (PET) agents for this application. We provide an overview of renal radionuclide PET radiotracers, in particular focusing on novel 18F-labelled and 68Ga-labelled agents. Several reported PET imaging probes allow assessment of glomerular filtration rate, such as [68Ga]ethylenediaminetetraacetic acid ([68Ga]EDTA), [68Ga]IRDye800-tilmanocept and 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS)). The diagnostic performance of [68Ga]EDTA has already been demonstrated in a clinical trial. [68Ga]IRDye800-tilmanocept shows receptor-mediated binding to glomerular mesangial cells, which in turn may allow the monitoring of progression of diabetic nephropathy. [18F]FDS shows excellent kidney extraction and excretion in rats and, as has been shown in the first study in humans. Further, due to its simple one-step radiosynthesis via the most frequently used PET radiotracer 2-deoxy-2-[18F]fluoro-d-glucose, [18F]FDS could be available at nearly every PET centre. A new PET radiotracer has also been introduced for the effective assessment of plasma flow in the kidneys: Re(CO)3-N-([18F]fluoroethyl)iminodiacetic acid (Re(CO)3([18F]FEDA)). This compound demonstrates similar pharmacokinetic properties to its 99mTc-labelled analogue [99mTc](CO)3(FEDA). Thus, if there is a shortage of molybdenum-99, Re(CO)3([18F]FEDA would allow direct comparison with previous studies with 99mTc. The PET radiotracers for renal imaging reviewed here allow thorough evaluation of kidney function, with the tremendous advantage of precise anatomical coregistration with simultaneously acquired CT images and rapid three-dimensional imaging capability

The utilization of positron emission tomography in the evaluation of renal health and disease

Purpose: Positron emission tomography (PET) is a nuclear imaging technique that uses radiotracers to visualize metabolic processes of interest across different organs, to diagnose and manage diseases, and monitor therapeutic response. This systematic review aimed to characterize the value of PET for the assessment of renal metabolism and function in subjects with non-oncological metabolic disorders. Methods: This review was conducted and reported in accordance with the PRISMA statement. Research articles reporting “kidney” or “renal” metabolism evaluated with PET imaging between 1980 and 2021 were systematically searched in Medline/PubMed, Science Direct, and the Cochrane Library. Search results were exported and stored in RefWorks, the duplicates were removed, and eligible studies were identified, evaluated, and summarized. Results: Thirty reports met the inclusion criteria. The majority of the studies were prospective (73.33%, n = 22) in nature. The most utilized PET radiotracers were 15O-labeled radio water (H215O, n = 14) and 18F-fluorodeoxyglucose (18F-FDG, n = 8). Other radiotracers used in at least one study were 14(R,S)-(18)F-fluoro-6-thia-heptadecanoic acid (18F-FTHA), 18F-Sodium Fluoride (18F-NaF), 11C-acetate, 68-Gallium (68Ga), 13N-ammonia (13N-NH3), Rubidium-82 (82Rb), radiolabeled cationic ferritin (RadioCF), 11C‐para-aminobenzoic acid (11C-PABA), Gallium-68 pentixafor (68Ga-Pentixafor), 2-deoxy-2-F-fluoro-d-sorbitol (F-FDS) and 55Co-ethylene diamine tetra acetic acid (55Co-EDTA). Conclusion: PET imaging provides an effective modality for evaluating a range of metabolic functions including glucose and fatty acid uptake, oxygen consumption and renal perfusion. Multiple positron emitting radiolabeled racers can be used for renal imaging in clinical settings. PET imaging thus holds the potential to improve the diagnosis of renal disorders, and to monitor disease progression and treatment response

Development of novel imaging biomarkers using positron emission tomography for characterization of malignant phenotype and response evaluation

Positron emission tomography (PET) enables noninvasive tumour imaging, as changes in metabolic activity secondary to therapy can be measured before changes in tumour size are evident on standard anatomic imaging. Two imaging approaches representing proliferation dependent and independent technologies are evolving as potential methods for assessing growth signalling and, thus, treatment response: [18F]3’-deoxy-3’-fluorothymidine (FLT) and [11C]choline. The validity of the former in patients with pancreatic cancer is unproven and likewise, the role of the latter in response to androgen deprivation/radiotherapy in prostate cancer (PCa) remains unexplored. Using a variety of approaches, the aim of this thesis was to provide an understanding of the role of these tracers in lesion detection and response assessment in patients by PET/computed tomography (PET/CT). Given the high physiological hepatic localisation of FLT, a recently reported kinetic spatial filtering (KSF) algorithm was evaluated as a way to de-noise abdominal FLT-PET data from patients with advanced pancreatic cancer. Application of KSF led to improved lesion detection. FLT uptake (SUV60,max) significantly increased in mid-treatment (gemcitabine based) progressors (p=0.04). In this limited number of patients, reduction in FLT uptake did not predict overall survival. The role of [11C]choline PET/CT in lesion detection and response in prostate cancer (PCa) was also investigated using semi-quantitative and quantitative methods. As a prelude to the quantitative imaging studies, it was established that irreversible tracer uptake characterised tumour (breast cancer) [11C]choline kinetics. Similar irreversible uptake characterised PCa. An important finding was that tumour [11C]choline uptake (in 29 PCa patients) correlated with choline kinase (CHK) expression but not proliferation, as assessed by Ki67 labelling index. Immunohistochemistry of the above patients’ prostate cores with CHKα antibody demonstrated a spectrum of CHKα expression, ranging from expression in prostatic-intraepithelial-neoplasia to low to high expression in malignant cores. These findings were further corroborated in a larger cohort of 75 malignant cores derived from non-imaging studies. Having established [11C]choline as a proliferation independent marker of growth, its role in assessing treatment response was investigated. [11C]choline PET was sensitive to metabolic changes within prostate tumours following androgen deprivation and radical radiotherapy. While promising data were obtained with [11C]choline PET, the radiotracer is subject to metabolic degradation complicating data analysis. To this end, a novel metabolically stable analogue of choline ([18F]fluoromethyl-[1,2-2H4]-choline ([18F]D4FCH)) was transitioned into volunteers and patients to study its pharmacokinetics and preliminary diagnostic potential. This tracer embodies deuterium isotope substitution as a means to discourage systemic metabolism. The radiotracer had favourable dosimetry (effective-dose: 0.025mSv/MBq) and safety. Preliminary results in non-small cell lung cancer showed that the tracer is taken up in tumours. Further studies are warranted to characterise this new tracer in different tumour types. As a prelude to imaging cancer cell death in tumours, a caspase-3 specific radiotracer, [18F](S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2(2,4- difluorophenoxymethyl)-pyrrolidine-1-sulfonyl) isatin ([18F]ICMT-11) was also transitioned into volunteers. The radiotracer had favourable dosimetry (effective-dose: 0.025mSv/MBq) and safety. In summary, FLT-PET/CT combined with KSF and [11C]choline PET/CT were shown to be promising methods for imaging early treatment response in patients. Further work will be required to evaluate the clinical relevance of these data in terms of overall patient outcome. Furthermore, a new choline-based radiotracer and a caspase-3 specific radiotracer have been transitioned into humans.Open Acces